title: Multimerized CHR-derived peptides as HIV-1 fusion inhibitors.
abstract: To date, several HIV-1 fusion inhibitors based on the carboxy-terminal leucine/isoleucine heptad repeat (CHR) region of an HIV-1 envelope protein gp41 have been discovered. We have shown that a synthetic peptide mimetic of a trimer form of the CHR-derived peptide C34 has potent inhibitory activity against the HIV-1 fusion mechanism, compared to a monomer C34 peptide. The present study revealed that a dimeric form of C34 is evidently structurally critical for fusion inhibitors, and that the activity of multimerized CHR-derived peptides in fusion inhibition is affected by the properties of the unit peptides C34, SC34EK, and T20. The fluorescence-based study suggested that the N36-interactive sites of the C34 trimer, including hydrophobic residues, are exposed outside the trimer and that trimerization of C34 caused a remarkable increase in fusion inhibitory activity. The present results could be useful in the design of fusion inhibitors against viral infections which proceed via membrane fusion with host cells.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Nomura
authors.forename: Chie
authors.initials: C
authors.lastname: Hashimoto
authors.forename: Takaharu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Nami
authors.initials: N
authors.lastname: Ohashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Murakami
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D057809:HEK293 Cells; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; C407149:peptide C34